A possible role of crustacean cardioactive peptide in regulating immune response in hepatopancreas of mud crab

Crustacean cardioactive peptide (CCAP), a cyclic amidated non-apeptide, is widely found in arthropods. The functions of CCAP have been revealed to include regulation of heart rate, intestinal peristalsis, molting, and osmotic pressure. However, to date, there has not been any report on the possible involvement of CCAP in immunoregulation in crustaceans. In this study, a CCAP precursor (designated as Sp-CCAP) was identified in the commercially important mud crab Scylla paramamosain, which could be processed into four CCAP-associated peptides and one mature peptide (PFCNAFTGC-NH2). Bioinformatics analysis indicated that Sp-CCAP was highly conserved in crustaceans. RT-PCR results revealed that Sp-CCAP was expressed in nerve tissues and gonads, whereas the Sp-CCAP receptor gene (Sp-CCAPR) was expressed in 12 tissues of S. paramamosain, including hepatopancreas. In situ hybridization further showed that an Sp-CCAPR-positive signal is mainly localized in the F-cells of hepatopancreas. Moreover, the mRNA expression level of Sp-CCAPR in the hepatopancreas was significantly up-regulated after lipopolysaccharide (LPS) or polyriboinosinic polyribocytidylic acid [Poly (I:C)] challenge. Meanwhile, the mRNA expression level of Sp-CCAPR, nuclear transcription factor NF-kappa B homologs (Sp-Dorsal and Sp-Relish), member of mitogen-activated protein kinase (MAPK) signaling pathway (Sp-P38), pro-inflammatory cytokines factor (Sp-TNFSF and Sp-IL16), and antimicrobial peptide (Sp-Lysozyme, Sp-ALF, Sp-ALF4, and Sp-ALF5) in the hepatopancreas were all up-regulated after the administration of synthetic Sp-CCAP mature peptide both in vivo and in vitro. The addition of synthetic Sp-CCAP mature peptide in vitro also led to an increase in nitric oxide (NO) concentration and an improved bacterial clearance ability in the hepatopancreas culture medium. The present study suggested that Sp-CCAP signaling system might be involved in the immune responses of S. paramamosain by activating immune molecules on the hepatopancreas. Collectively, our findings shed new light on neuroendocrine-immune regulatory system in arthropods and could potentially provide a new strategy for disease prevention and control for mud crab aquaculture

Associations of Household Solid Fuel Use With Falls and Fall-Related Injuries in Middle-Aged and Older Population in China: A Cohort Study

Objective: This study evaluated the associations of solid fuels with incidence of falls and fall-related injuries.Methods: Data were taken from wave 1∼4 of the China Health and Retirement Longitudinal Study, including 15,651 participants aged 45 years and older. Modified Poisson regression was used to examine the associations of solid fuels with falls and fall-related injuries.Results: Modified Poisson regression analysis showed that solid fuels users for cooking had an increasing incidence of falls and fall-related injuries, with RR of 1.211 (95% CI: 1.124, 1.305) and 1.248 (95% CI: 1.107, 1.408); for heating had an incidence, with RR of 1.178 (95% CI: 1.062, 1.306) and 1.134 (95% CI: 0.963, 1.335); combined for cooking and heating, with RR of 1.247 (95% CI: 1.105, 1.408) and 1.185 (95% CI: 0.982, 1.431).Conclusion: Our study suggests that solid fuel use is associated with a higher incidence of falls and fall-related injuries among adults aged 45 years and older in China. It is necessary to restrict solid fuel use to reduce household air pollution and make stronger environmental protection policies to improve household environment

Adenoid lymphocyte heterogeneity in pediatric adenoid hypertrophy and obstructive sleep apnea

IntroductionAdenoid hypertrophy is the main cause of obstructive sleep apnea in children. Previous studies have suggested that pathogenic infections and local immune system disorders in the adenoids are associated with adenoid hypertrophy. The abnormalities in the number and function of various lymphocyte subsets in the adenoids may play a role in this association. However, changes in the proportion of lymphocyte subsets in hypertrophic adenoids remain unclear.MethodsTo identify patterns of lymphocyte subsets in hypertrophic adenoids, we used multicolor flow cytometry to analyze the lymphocyte subset composition in two groups of children: the mild to moderate hypertrophy group (n = 10) and the severe hypertrophy group (n = 5).ResultsA significant increase in naïve lymphocytes and a decrease in effector lymphocytes were found in severe hypertrophic adenoids.DiscussionThis finding suggests that abnormal lymphocyte differentiation or migration may contribute to the development of adenoid hypertrophy. Our study provides valuable insights and clues into the immunological mechanism underlying adenoid hypertrophy

Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis

The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry. One sample had a surface topography at micron-scale (TCP-B, with a bigger surface structure dimension) whilst the other had a surface topography at submicron scale (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic differentiation factors, human bone marrow stromal cells (hBMSCs) were more spread on TCP-S than on TCP-B with alterations in actin organization and increased primary cilia prevalence and length. The cilia elongation on TCP-S was similar to that observed on glass in the presence of osteogenic media and was followed by recruitment of transforming growth factor-β RII (p-TGFβ RII) to the cilia axoneme. This was associated with enhanced osteogenic differentiation of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression for key osteogenic markers in the absence of additional osteogenic growth factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs, TCP-S induced bone formation while TCP-B did not. It is most likely that the surface topography of calcium phosphate ceramics regulates primary cilia length and ciliary recruitment of p-TGFβ RII associated with osteogenesis and bone formation. This bioengineering control of osteogenesis via primary cilia modulation may represent a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery applications. Statement of Significance The surface topography of synthetic biomaterials plays important roles in material-driven osteogenesis. The data presented herein have shown that the surface topography of calcium phosphate ceramics regulates mesenchymal stromal cells (e.g., human bone marrow mesenchymal stromal cells, hBMSCs) with respect to morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation in vitro. Together with bone formation in vivo, our results suggested a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery by the bioengineering control of osteogenesis via primary cilia modulation

JunD/AP-1-Mediated Gene Expression Promotes Lymphocyte Growth Dependent on Interleukin-7 Signal Transduction

Interleukin-7 (IL-7) is an essential cytokine for lymphocyte growth that has the potential for promoting immune reconstitution. This feature makes IL-7 an ideal candidate for therapeutic development. As with other cytokines, signaling through the IL-7 receptor induces the JAK/STAT pathway. However, the broad scope of IL-7 regulatory targets likely necessitates the use of other signaling components whose identities remain poorly defined. To this end, we used an IL-7 dependent T-cell line to examine how expression of the glycolytic enzyme, Hexokinase II (HXKII) was regulated by IL-7 in a STAT5-independent manner. Our studies revealed that IL-7 promoted the activity of JNK (Jun N-terminal Kinase), and that JNK, in turn, drove the expression of JunD, a component of the Activating Protein 1 (AP-1) transcription factors. Gel shifts showed that the AP-1 complex induced by IL-7 contained JunD but not c-Fos or c-Jun. Inhibition of JNK/JunD blocked glucose uptake and HXKII gene expression, indicating that this pathway was responsible for promoting HXKII expression. Because others had shown that JunD was a negative regulator of cell growth, we performed a bioinformatics analysis to uncover possible JunD-regulated gene targets. Our search revealed that JunD could control the expression of proteins involved in signal transduction, cell survival and metabolism. One of these growth promoters was the oncogene, Pim-1. Pim-1 is an IL-7-induced protein that was inhibited when the activities of JNK or JunD were blocked, showing that in IL-7 dependent T-cells JunD can promote positive signals transduced through Pim-1. This was confirmed when the IL-7-induced proliferation of CD8 T-cells was impaired upon JunD inhibition. These results show that engagement of the IL-7 receptor drives a signal that is more complex than the JAK/STAT pathway, activating JNK and JunD to induce rapid growth stimulation through the expression of metabolic and signaling factors like HXKII and Pim-1

Bat-Derived Influenza Hemagglutinin H17 Does Not Bind Canonical Avian or Human Receptors and Most Likely Uses a Unique Entry Mechanism

A new influenza-like virus genome (H17N10) was recently discovered in bats and offers a new perspective about the origin and evolution of influenza viruses. The viral envelope glycoprotein hemagglutinin (HA) is responsible for influenza virus receptor binding, fusion, and entry into the cell; therefore, the structure and function of HA H17 was characterized. The 2.70 Å resolution crystal structure revealed that H17 has a typical influenza A virus HA fold, but with some special features, including a distorted putative sialic acid (SA) binding site and low thermostability. No binding to either the canonical human α2,6 SA-linkage or avian α2,3 SA-linkage receptor was observed. Furthermore, H17 glycan binding was not detected using a chip covering more than 600 glycans. Our results demonstrate that H17 is unique among characterized HAs and that the bat-derived influenza virus may use a different entry mechanism compared to canonical influenza viruses

Aloe Vera-Fermented Beverage Ameliorates Obesity and Gut Dysbiosis in High-Fat-Diet Mice

Aloe vera has been proven to have various medicinal properties, including anti-inflammatory and anti-obesity functions. However, the effects of Aloe vera-fermented beverages (AFB) on obesity and its complications are still not clear. In this study, HepG2 cells in high-fat environment and high-fat diet (HFD) mice were used to investigate the potential obesity-preventing function of AFB. We found that AFB intervention decreased the amount of lipid droplets of HepG2 cells, suppressed the body weight gain and adipose accumulation, and reduced the serum contents of total cholesterol (TC), alanine aminotransferase (ALT), and interleukin 10 (IL-10) of HFD-mice. In addition, it also changed the composition of the gut microbiota. The ratio of Firmicutes/Bacteroidetes was decreased, while the relative abundance of Muribaculaceae, Alistipes and Rikenellaceae RC9_gut_group was increased after the administration of AFB compared with HFD-mice. These results demonstrated that AFB can prevent diet-induced obesity (DIO) and provides a new option to modulate obesity-related gut dysbiosis

Aloe Vera-Fermented Beverage Ameliorates Obesity and Gut Dysbiosis in High-Fat-Diet Mice

Aloe vera has been proven to have various medicinal properties, including anti-inflammatory and anti-obesity functions. However, the effects of Aloe vera-fermented beverages (AFB) on obesity and its complications are still not clear. In this study, HepG2 cells in high-fat environment and high-fat diet (HFD) mice were used to investigate the potential obesity-preventing function of AFB. We found that AFB intervention decreased the amount of lipid droplets of HepG2 cells, suppressed the body weight gain and adipose accumulation, and reduced the serum contents of total cholesterol (TC), alanine aminotransferase (ALT), and interleukin 10 (IL-10) of HFD-mice. In addition, it also changed the composition of the gut microbiota. The ratio of Firmicutes/Bacteroidetes was decreased, while the relative abundance of Muribaculaceae, Alistipes and Rikenellaceae_RC9_gut_group was increased after the administration of AFB compared with HFD-mice. These results demonstrated that AFB can prevent diet-induced obesity (DIO) and provides a new option to modulate obesity-related gut dysbiosis

Spinal voltage-gated potassium channel Kv1.3 contributes to neuropathic pain via promotion of microglial M1 polarization and activation of the NLRP3 inflammasome.

Background: Studies have shown that activation of microglia is the main mechanism of neuropathic pain. The Kv1.3 channel is a novel therapeutic target for treating neuroinflammatory disorders due to its crucial role in subsets of microglial cells. As such, it may be involved in the processes of neuropathic pain, however, whether Kv1.3 plays a role in neuroinflammation following peripheral nerve injury is unclear. Methods: The spared nerve injury model (SNI) was used to establish neuropathic pain. Western blot and immunofluorescence were used to examine the effect of Kv1.3 in the SNI rats. PAP-1, a Kv1.3 specific blocker was administered to alleviate neuropathic pain in the SNI rats. Results: Neuropathic pain and allodynia occurred after SNI, the levels of M1 (CD68, iNos) and M2 (CD206, Arg-1) phenotypes were up-regulated in the spinal cord, and the protein levels of NLRP3, caspase-1 and IL-1β were also increased. Pharmacological blocking of Kv1.3 with PAP-1 alleviated hyperpathia induced by SNI. Meanwhile, intrathecal injection of PAP-1 reduced M1 polarization and decreased NLRP3, caspase-1, and IL-1β expressions of protein levels. Conclusion: Our research indicates that the Kv1.3 channel in the spinal cord contributes to neuropathic pain by promoting microglial M1 polarization and activating the NLRP3 inflammasome

Aloe Vera-Fermented Beverage Ameliorates Obesity and Gut Dysbiosis in High-Fat-Diet Mice

Aloe vera has been proven to have various medicinal properties, including anti-inflammatory and anti-obesity functions. However, the effects of Aloe vera-fermented beverages (AFB) on obesity and its complications are still not clear. In this study, HepG2 cells in high-fat environment and high-fat diet (HFD) mice were used to investigate the potential obesity-preventing function of AFB. We found that AFB intervention decreased the amount of lipid droplets of HepG2 cells, suppressed the body weight gain and adipose accumulation, and reduced the serum contents of total cholesterol (TC), alanine aminotransferase (ALT), and interleukin 10 (IL-10) of HFD-mice. In addition, it also changed the composition of the gut microbiota. The ratio of Firmicutes/Bacteroidetes was decreased, while the relative abundance of Muribaculaceae, Alistipes and Rikenellaceae RC9_gut_group was increased after the administration of AFB compared with HFD-mice. These results demonstrated that AFB can prevent diet-induced obesity (DIO) and provides a new option to modulate obesity-related gut dysbiosis